Integrating basic radiobiological science and epidemiological studies: why and how

There is quite an extensive set of epidemiology studies conducted for a range of different radiation exposure scenarios and in some cases at doses that can be considered to be in the low dose range (<100 mGy). In addition, there is an extensive literature on the effects of radiation at animal and cellular levels, as well as expanding knowledge of the underlying mechanisms of disease formation (both cancer and non-cancer). A significant concern is that these two areas of study have been linked rarely to support each other-to enhance low dose/low dose-rate extrapolation and reduction of uncertainty in risk estimates. Research should provide specific types of data to support the epidemiology and thereby enhance the radiation risk assessment process. Such an approach is one that can be adapted from that used for chemical exposures. It is based on the concept of adverse outcome pathways for the formation of adverse health outcomes. The adverse outcome pathway conceptual framework is considered to be a logical sequence of events (so-called key events) or processes within biological systems that can be used to understand adverse effects and refine the current risk assessment practice. This approach, which has only been used currently for chemicals, shifts the risk assessment focus from traditional apical endpoints (e.g., cancer and cardiovascular disease) to the development of a mechanistic understanding of effects at a molecular and cellular level. The need is to further the knowledge of the key events in radiation-induced diseases and to provide information on the dose and dose-rate response for these. It is proposed that the key-event approach be used in conjunction with enhanced radiation epidemiology data to reduce overall uncertainty in low dose/low dose-rate cancer and non-cancer risk estimates.